Integrated Formulation and Thermal Modulation Strategies for Enhancing Anti-Inflammatory Transdermal Delivery of Dracorhodin and Ketoprofen

Transdermal patches are widely used for local anti-inflammatory therapy, but their delivery efficiency is often limited by the barrier function of the stratum corneum. This study aimed to develop an optimized dracorhodin transdermal patch and to evaluate temperature-controlled heating as a physical enhancement strategy using ketoprofen patches as a representative anti-inflammatory model. Dracorhodin ethanol extract was prepared by ethanol extraction and rotary evaporation, and a high-performance liquid chromatography method was established for quantitative analysis. Azone, isopropyl myristate, and acrylate pressure-sensitive adhesive were screened as key excipients, and dracorhodin patches were prepared using a coating method. The optimized patches were evaluated for appearance, content uniformity, adhesion, in vitro skin permeation, and anti-inflammatory activity using an egg white-induced rat paw swelling model. Meanwhile, the effects of heating temperature and heating duration on ketoprofen patch permeation were investigated using in vitro skin permeation experiments, in vivo fluorescence imaging, and pharmacokinetic analysis. The optimized dracorhodin patch formulation contained 19.6% azone, 11.5% isopropyl myristate, and 47.1% pressure-sensitive adhesive. The three batches of patches showed uniform appearance, acceptable content uniformity, stable adhesion, and a cumulative permeation amount of 13–20 μg/cm² within 28 h. In vivo pharmacodynamic evaluation showed that the dracorhodin patch produced a swelling inhibition rate of 62.18% at 4 h, approaching that of the ketoprofen positive control. For ketoprofen patches, temperature-controlled heating significantly enhanced transdermal permeation, with the permeation rate increasing from 10.11 to 20.56 μg/cm²·h as the heating temperature increased from 33°C to 45°C. Heating for 90 min at 40°C provided an effective balance between permeation enhancement and practical application. Fluorescence imaging and pharmacokinetic results further confirmed that thermal treatment improved drug diffusion and systemic exposure. These findings suggest that formulation optimization and temperature-controlled physical enhancement are complementary strategies for improving anti-inflammatory transdermal patch delivery and may provide a basis for the development of advanced patch-based drug-device combination products.